Objective: The development and application of methodology by which biological macromolecules and their aggregates may be visualized at the limit of resolution of electron microscopy, in a state which approximates that in solution in the biological system of origin. Current applications are in the areas of glycoprotein structure (CEA, cell surface glycoproteins, blood group substances), ribonucleoprotein structure (ribosomes, chromatin), muscle structure, and blood clotting. Approach: Macromolecular electron microscopy is applied to purified fractions in conjunction with other physical methods, as illustrated below.